Paraneoplastic Kelch-like protein 11 antibody-associated cerebellar and limbic encephalitis caused by metastatic "burned-out" seminoma - A scar(r)y phenomenon.

INTRODUCTION: The diagnosis of paraneoplastic neurologic syndromes is challenging when the primary tumor masquerades as scar tissue (i.e. "burned-out"). METHODS: Case report. RESULTS: A 45-year-old male patient presented with progressive cerebellar symptoms and hearing loss. Initial screening for malignancy and extensive testing of paraneoplastic and autoimmune neuronal antibodies gave negative results. Repeated whole-body FDG-PET CT revealed a single paraaortic lymphadenopathy, metastasis of a regressed testicular seminoma. Anti-Kelch-like protein-11 (KLHL11) encephalitis was finally diagnosed. CONCLUSION: Our case highlights the importance of continued efforts to find an often burned-out testicular cancer in patients with a highly unique clinical presentation of KLHL11 encephalitis.

Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer.

OBJECTIVE: Although targeted approaches have become available in second- and third-line settings, platinum-based chemotherapy remains the standard first-line treatment for advanced muscle-invasive bladder cancer (MIBC). Therefore, the prediction of platinum resistance is of utmost clinical importance. METHODS: In this study, we established a routine compatible method for the molecular classification of MIBC samples according to various classification systems and applied this method to evaluate the impact of subtypes on survival after adjuvant chemotherapy. This retrospective study included 191 patients with advanced MIBC (pT≥3 or pN+) who underwent radical cystectomy, with or without adjuvant chemotherapy. A 48-gene panel and classifier rule set were established to determine molecular subtypes according to TCGA, MDA, LundTax, and Consensus classifications. Additionally, 12 single platinum-predictive candidate genes were assessed. The results were correlated with patients' clinicopathological and follow-up data and were validated using independent data sets. RESULTS: Our final evaluation of 159 patients demonstrated better survival in the luminal groups for those who received chemotherapy compared with those who did not. In contrast, no such differences were observed in basal subtypes. The use of chemotherapy was associated with better survival in patients with high APOBEC3G expression (p < 0.002). This association was confirmed using an independent data set of patients who received neoadjuvant platinum therapy. CONCLUSIONS: The proposed method robustly replicates the most commonly used transcriptome-based subtype classifications from paraffin-embedded tissue samples. The luminal, but not basal, molecular subtypes had the greatest benefit from adjuvant platinum therapy. We identified and validated APOBEC3G as a novel predictive marker for platinum-treated patients.

Addition of Chromosome 17 Polysomy and HER2 Amplification Status Improves the Accuracy of Clinicopathological Factor-Based Progression Risk Stratification and Tumor Grading of Non-Muscle-Invasive Bladder Cancer.

Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) significantly worsens life expectancy. Its risk can be assessed by clinicopathological factors according to international guidelines. However, additional molecular markers are needed to refine and improve the prediction. Therefore, in the present study, we aimed to predict the progression of NMIBCs to MIBC by assessing p53 expression, polysomy of chromosome 17 (Chr17) and HER2 status in the tissue specimens of the tumors of 90 NMIBC patients. Median follow-up was 77 months (range 2−158). Patients with Chr17 polysomy or HER2 gene amplification had a higher rate of disease progression (hazard ratio: 7.44; p < 0.001 and 4.04; p = 0.033, respectively; univariate Cox regression). Multivariable Cox regression models demonstrated that the addition of either Chr17 polysomy or HER2 gene amplification status to the European Association of Urology (EAU) progression risk score increases the c-index (from 0.741/EAU/ to 0.793 and 0.755, respectively), indicating that Chr17 polysomy/HER2 amplification status information improves the accuracy of the EAU risk table in predicting disease progression. HER2/Chr17 in situ hybridization can be used to select non-progressive cases not requiring strict follow-up, by reclassifying non-HER2-amplified, non-polysomic NMIBCs from the high- and very high-risk groups of EAU to the intermediate-risk group.

Radiomics analysis of contrast-enhanced CT scans can distinguish between clear cell and non-clear cell renal cell carcinoma in different imaging protocols.

Introduction: This study aimed to construct a radiomics-based machine learning (ML) model for differentiation between non-clear cell and clear cell renal cell carcinomas (ccRCC) that is robust against institutional imaging protocols and scanners. Materials and methods: Preoperative unenhanced (UN), corticomedullary (CM), and excretory (EX) phase CT scans from 209 patients diagnosed with RCCs were retrospectively collected. After the three-dimensional segmentation, 107 radiomics features (RFs) were extracted from the tumor volumes in each contrast phase. For the ML analysis, the cases were randomly split into training and test sets with a 3:1 ratio. Highly correlated RFs were filtered out based on Pearson's correlation coefficient (r > 0.95). Intraclass correlation coefficient analysis was used to select RFs with excellent reproducibility (ICC ≥ 0.90). The most predictive RFs were selected by the least absolute shrinkage and selection operator (LASSO). A support vector machine algorithm-based binary classifier (SVC) was constructed to predict tumor types and its performance was evaluated based-on receiver operating characteristic curve (ROC) analysis. The "Kidney Tumor Segmentation 2019" (KiTS19) publicly available dataset was used during external validation of the model. The performance of the SVC was also compared with an expert radiologist's. Results: The training set consisted of 121 ccRCCs and 38 non-ccRCCs, while the independent internal test set contained 40 ccRCCs and 13 non-ccRCCs. For external validation, 50 ccRCCs and 23 non-ccRCCs were identified from the KiTS19 dataset with the available UN, CM, and EX phase CTs. After filtering out the highly correlated and poorly reproducible features, the LASSO algorithm selected 10 CM phase RFs that were then used for model construction. During external validation, the SVC achieved an area under the ROC curve (AUC) value, accuracy, sensitivity, and specificity of 0.83, 0.78, 0.80, and 0.74, respectively. UN and/or EX phase RFs did not further increase the model's performance. Meanwhile, in the same comparison, the expert radiologist achieved similar performance with an AUC of 0.77, an accuracy of 0.79, a sensitivity of 0.84, and a specificity of 0.69. Conclusion: Radiomics analysis of CM phase CT scans combined with ML can achieve comparable performance with an expert radiologist in differentiating ccRCCs from non-ccRCCs.

[Pathology of tumors of the urinary bladder, aspects and expectations of the histological report (TUR, cystectomy)]. / Húgyhólyagtumorok patológiája, szövettani diagnózisának szempontjai, lehetoségei és elvárásai (TUR, cisztektómia).

Urothelial tumors are among the most frequently occurring malignancies. The patients' clinical outcome can be diverse after recognition of the presence of the tumor. The result of the histology report (grade, histologic subtype, stage) makes remarkable impact on treatment strategies. There are innumerable papers (debates) in the literature concerning the best methods in classification, stage determination, application of immunohistochemical markers (to possibly avoid false negative, false positive results) and the use of molecular biological examinations. The authors attempt to draw attention on the everyday diagnostic difficulties of the "general pathologist", through their own experience and the latest reports of the literature.

Accuracy of the preoperative diagnostic workup in patients with head and neck cancers undergoing neck dissection in terms of nodal metastases.

PURPOSE: The presence of cervical lymph node metastases is one of the most influential prognostic factors in head and neck squamous cell carcinomas. The management of clinically N0 neck in patients with head and neck cancer remains controversial: elective neck dissection has relatively high morbidity, adversely affecting the quality of life, however, abandoning elective neck dissection is known to compromise overall survival in numerous primaries. The purpose of this study was to evaluate the accuracy of the conventional imaging modalities (CT, MRI, US) and fine-needle aspiration cytology (FNAC) in the detection of lymph node metastases in the neck. METHODS: Sixty two patients were included in the study, who underwent primary tumor resection and neck dissection. Preoperative nodal status was compared with postoperative histopathology nodal status. In our retrospective study, we reviewed the patient documentation. Statistical analysis of the data-with descriptive statistics and correlation analysis-was performed with Chi-square test. RESULTS: The sensitivity of conventional imaging modalities and FNAC were 82.8% and 81.8%, respectively, while specificity were 73.9% and 100%, respectively. Positive predictive value calculated for imaging modalities and FNAC were 82.8%, 100%, respectively, while negative predictive values were 73.9% and 66.6%, respectively. CONCLUSION: Neither the sensitivity of imaging modalities (CT, MRI, US) nor FNAC reached 100%, none of these methods can definitively exclude the presence of regional tumor metastasis. According to these data, no permissive alteration should be allowed from the current guidelines (e.g. NCCN) based on imaging/FNAC examinations regarding the need for elective neck dissection.

MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients.

Chemotherapy resistance is a main cause of therapeutic failure and death in bladder cancer. With the approval of immune checkpoint inhibitors, prediction of platinum treatment became of great clinical importance. Matrix metalloproteinase-7 (MMP-7) was shown to be involved in cisplatin resistance. Therefore, tissue and circulating MMP-7 levels were evaluated in 124 bladder cancer patients who received postoperative platinum-based chemotherapy. Tissue MMP-7 levels were analyzed by immunohistochemistry in 72 formalin-fixed, paraffin-embedded chemo-naïve tumor samples, while MMP-7 serum concentrations were determined in 132 serum samples of an independent cohort of 52 patients. MMP-7 tissue and serum levels were correlated with clinicopathological and follow-up data. MMP-7 gene expression was determined by RT-qPCR in 20 urothelial cancer cell lines and two non-malignant urothelial cell lines. MMP-7 was overexpressed in RT-112 and T-24 cells by stable transfection, to assess its functional involvement in platinum sensitivity. High MMP-7 tissue expression and pretreatment serum concentrations were independently associated with poor overall survival (tissue HR = 2.296, 95%CI = 1.235-4.268 and p = 0.009; serum HR = 2.743, 95%CI = 1.258-5.984 and p = 0.011). Therefore, MMP-7 tissue and serum analysis may help to optimize therapeutic decisions. Stable overexpression in RT-112 and T-24 cells did not affect platinum sensitivity.

Development and Initial Testing of a Modified UroVysion-Based Fluorescence In Situ Hybridization Score for Prediction of Progression in Bladder Cancer.

OBJECTIVES: Our aim was to predict progression of non-muscle-invasive bladder urothelial carcinomas (NMIUCs) into muscle-invasive disease by assessing cytogenetic abnormality of tumors with a new UroVysion scoring system. METHODS: Seventy-five bladder cancer cases (including 57 NMIUCs) were classified according to the quantitatively assessed degree of UroVysion-detected chromosomal abnormalities into urine fluorescence in situ hybridization score (UFS) groups: UFS I, II, and III. Cox time-to-event, Kaplan-Meier, and C-statistics analyses were performed. RESULTS: UFS proved to be an independent prognostic factor of progression-free survival (PFS) and time to progression (TTP). NMIUCs with UFS III had a 34.05-fold increased hazard for progression to muscle-invasive cancer (TTP; 95% confidence interval, 5.841-198.5; P < .001) in comparison with UFS I to II cases. The addition of UFS to conventional risk scores increased the C-index for PFS and TTP. CONCLUSIONS: UFS can indicate an increased risk for progression into muscle-invasive disease in patients with NMIUC and improves prognostic accuracy of the current clinical risk assessment systems.

[Genetic testing of thyroid nodules using a gene panel developed on a new generation sequencing platform]. / A pajzsmirigygöbök genetikai vizsgálata újgenerációs szekvenáláson alapuló platformon kifejlesztett génpanel segítségével.

Introduction: Twenty-five percent of fine-needle aspiration biopsy samples of thyroid nodules produce indeterminate cytological results. Genetic testing of nodules can contribute to accurate diagnosis. Aim: Developing the first gene panel in Europe utilizing the 23 most relevant thyroid oncogenes with 568 mutations. Method: Examination of the isolated DNA from biopsy samples by Ion Torrent new generation sequencing. Results: The validation of our method was performed on tumor tissue samples, in which 127 genetic variations were identified, yet unknown in thyroid tumors. AXIN1 was the most polymorphic gene, while BRAF c.1799T>A (V600E) was the most frequently identified mutation. We detected 36 clinically relevant variants, 75% of which have not been described in the literature. Six of our 8 cytologically malignant and 8 of our 14 indeterminate as well as 20 of our 28 cytologically benign samples were identified as containing pathologic variants in a driver gene (BRAF c.1799T>A, NRAS c.181C>A). Conclusion: We have developed a validated, reliable new generation sequencing-based method with high positive predictive value (89%) and sensitivity (79%), suitable for the early detection of malignant lesions in the thyroid. Orv Hetil. 2019; 160(36): 1417-1425.

Validation of survivin and HMGA2 as biomarkers for cisplatin resistance in bladder cancer.

OBJECTIVES: Cisplatin-based chemotherapy represents the gold standard in the treatment of advanced bladder cancer (BC) both in the neoadjuvant and adjuvant setting. Since novel immunooncologic agents are available for cisplatin-resistant or ineligible patients, biological markers for the prediction of cisplatin resistance become more important in treatment decisions. Therefore, we aimed to assess the therapy predictive value of 8 promising tissue biomarkers with regard to cisplatin therapy. METHODS: Emmprin, survivin, HMGA2, MTA1, RhoGDI, PEG10, TGM2, and TLN1 expressions were analyzed in paraffin-embedded bladder cancer tissue samples of 106 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Results were correlated with the clinicopathological and follow-up data by performing both univariable and multivariable survival analyses. RESULTS: Higher HMGA2 nuclear staining intensity and positive survivin nuclear staining were associated with worse overall survival (OS) (P = 0.045 and P = 0.002, respectively). In accordance, survivin nuclear staining also significantly correlated with shorter progression free survival (PFS, P = 0.024), while HMGA2 nuclear positivity tended to correlate with shorter PFS (P = 0.069) after at least 2 cycles of chemotherapy. In the multivariable analyses only survivin remained as an independent predictor of both OS and PFS (P = 0.008 and P = 0.025). None of the other markers proved to be significant predictors of adjuvant or salvage cisplatin-based chemotherapy. CONCLUSIONS: Our results demonstrate that survivin represents a promising marker for the prediction of cisplatin resistance in BC. In addition the therapy predictive role of HMGA2 should be further investigated. Immunohistochemical analysis of BC samples provides a feasible way for the prediction of cisplatin-resistance and may therefore provide a valuable tool for optimizing treatment decisions in advanced BC.

[Mucosal melanoma primary and metastatic cases with urogenital localization in our department]. / Urogenitalis lokalizációjú mucosamelanoma primer és áttétes esetei klinikánkon.

INTRODUCTION: Both primary and metastatic cases of mucosal melanoma in urogenital localization are rare tumors. Only 4-5% of all primary melanomas do not arise from the skin. Extracutaneous melanomas have a complex clinical presentation, but these aggressive tumors have a poor prognosis. MATERIALS AND METHOD: In our department, we found 7 patients with malignant melanoma of the genitourinary tract in the past few years. The 7 cases were: primary amelanotic melanoma of the female urethra, a primary melanoma of the bladder, two primary melanomas of the penis, a metastatic melanoma of the urethra and another to the testis and a metastatic melanoma of the bladder with melanuria. We retrospectively analyzed the available data to describe the presentation, management, and clinical outcome of the patients. RESULTS: In the three inoperative cases, palliative, urologic surgical procedures and systemic antitumor therapy were performed. Two of the four primary urogenital tumors were localized to the penis. In one case, local recurrence developed after surgical treatment, but with a radical, repeated surgery, the patient has been asymptomatic for a year and a half. In the other, neglected case, the penis melanoma spread through the urethra and the inguinal lymph nodes two years after radical surgery and inguinal block dissection. In the female primary urethral melanoma case, the first histological study reported a primary mesenchymal tumor, and the recurrent tumor that occurred one and a half years later showed melanoma diagnosis. Radical surgery performed because of urethral involvement resulted in a 5-year asymptomatic state, followed by local recurrence and distant metastasis. In the fourth case of a primary bladder melanoma, the rapid progression of the disease and the BRAF positivity of the tumor suggested that not the firstly diagnosed bladder melanoma was the primary tumor. CONCLUSION: The occurrence of urinary tract melanoma is very rare and its discovery happens often in a disseminated state, so the expected prognosis of the cases is also poor. The most important factors for increasing therapeutic efficacy are early diagnosis and radical surgical intervention. Tumors appearing in different localizations require different urological surgical approaches. The literature recommendations for treatment are not uniform. Their prognosis is worse compared to the cutaneous melanoma, which may be due to clinical and pathological diagnostic difficulties. The latest targeted and immunotherapeutic agents can significantly improve the survival of metastatic patients. Orv Hetil. 2019; 160(10): 378-385.

PREDICTIVE VALUE OF SOMATIC MUTATIONS FOR THE DEVELOPMENT OF MALIGNANCY IN THYROID NODULES BY CYTOPATHOLOGY.

OBJECTIVE: The purpose of our prospective longitudinal study was to evaluate the predictive efficacy of genetic testing for malignancies in fine-needle aspiration biopsy samples that are cytologically benign at the time of biopsy. METHODS: A total of 779 aspirated cytological samples collected from thyroid nodules of 626 patients were included in a 3-year follow-up study. Consecutive patients with cytologically benign thyroid nodules by the Bethesda System for Reporting Thyroid Cytopathology were enrolled in the study. At enrollment, somatic 1-point nucleotide polymorphisms of BRAF and RAS family genes were tested by melting-point analysis, while RET/PTC and PAX8/PPAR-gamma rearrangements were examined by real-time polymerase chain reaction. The genetic test was considered to be positive if a somatic mutation was found. Malignant cytopathologic diagnoses were confirmed by histopathology. RESULTS: In samples collected from 779 thyroid nodules, there were 39 BRAF, 33 RAS mutations, and 1 RET/PTC rearrangements found at the beginning of the study. No PAX8/PPAR-gamma rearrangement was identified. There were 52 malignant thyroid tumors removed during follow-up, out of which 24 contained a somatic mutation. The specificity of the presence of somatic mutations for malignancies was as high as 93.3%, and sensitivity was 46.2%. The negative predictive value of genetic testing reached 96.0%. CONCLUSION: Our results show that our set of genetic tests can predict the appearance of malignancy in benign thyroid nodules (at the beginning of follow-up) with high specificity and strong negative predictive value. ABBREVIATIONS: BRAF = v-raf murine sarcoma viral oncogene homolog B1 FLUS = follicular lesion of undetermined significance FNAB = fine-needle aspiration biopsy FTC = follicular thyroid carcinoma HRAS = homologous to the oncogene from the Harvey rat sarcoma virus KRAS = homologous to the oncogene from the Kirsten rat sarcoma virus NRAS = first isolated from a human neuroblastoma/neuroblastoma RAS = viral oncogene homolog PAX8 = paired box 8 PCR = polymerase chain reaction PPAR-gamma = peroxisome proliferator-activated receptor gamma PTC = papillary thyroid carcinoma RAS = rat sarcoma RET = rearranged during transfection tyrosine-kinase proto-oncogene SM = somatic mutation SNP = single-nucleotide polymorphism.

Reliability of immunocytochemistry and fluorescence in situ hybridization on fine-needle aspiration cytology samples of breast cancers: A comparative study.

INTRODUCTION: To characterize breast tumors and metastases, fine-needle aspiration cytology (FNAB) can be a favorable first choice. However, the diagnostic accuracy of ancillary tests applied to FNAB samples is yet to be validated. PATIENTS AND METHODS: We examined 110 breast cancer patients' paired cytological and surgical resection specimens evaluated between 2005 and 2014. Comparison of ER and Her2 immunocytochemical (ICC) and immunohistochemical (IHC) staining and HER2 fluorescence in situ hybridization (FISH) was performed. RESULTS: Significant difference (p < 0.001) and moderate correlation (κ = 0.446) were noted between results of 97 paired ICC an IHC reactions for ER expression. ICC for ER status had a sensitivity of 75%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 38.2%. Significant difference (p = 0.012) and moderate correlation (κ = 0.541) were found between results of 77 paired ICC an IHC reactions for Her2 expression. The Her2 ICC had a sensitivity of 54%, specificity of 95.4%, PPV of 66.7%, and NPV of 92.6%. The results of FISH carried out on 23 paired samples of FNAB and surgical specimens indicated perfect correlation (κ = 1.000) and no significant difference (p = 1.000). FISH performed on FNAB has sensitivity, specificity, PPV, and NPV of 100%. CONCLUSION: The correlation of ICC and IHC is moderate regarding ER and Her2 expression of the same tumor. FISH performed on FNAB samples is suitable to categorize primary and metastatic breast cancer in regard of HER2 gene amplification status and can be used as a predictive test in respect of therapies targeting HER2. Diagn. Cytopathol. 2016;44:466-471. © 2016 Wiley Periodicals, Inc.

[A giant myxoid leiomyoma mimicking an inguinal hernia]. / Lágyéksérvet utánzó gigantikus méretu myxoid leiomyoma.

Leiomyoma is a rare, smooth muscle tumour that can occur everywhere in the human body. The authors present the history of a 60-year-old female, who had a giant, Mullerian type myxoid leiomyoma in the inguinal region mimicking acute abdominal symptoms. After examination the authors removed the soft tissue mass in the right femoral region reaching down in supine position to the middle third of the leg measuring 335 × 495 × 437 mm in greatest diameters in weight 33 kg. Reconstruction of the tissue defect was performed using oncoplastic guidelines. During the follow-up time no tumour recurrence was detected and the quality of life of the patient improved significantly.

Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.

The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature.

[The role of aspiration cytology in tumor diagnostics]. / Az aspirációs citológia szerepe a daganatdiagnosztikában.

Fine needle aspiration biopsy (FNAB) of focal lesions is a quick, relatively simple and cost-effective diagnostic method. However, performing aspirations and interpreting smears require skill and experience. Before initiating an aspiration the doctor needs to be aware of the limits of cytology as it is vital to know what kind of diagnostic issues can be answered upon a smear and what kind of questions cannot. Traditionally FNAB was performed without radiologic guidance, and therefore almost only palpable lesions were aspirated. Since ultrasound (US) has become widely used in medicine, it is axiomatical that FNAB is ideally performed with US guidance not only for the protection of the patients but also for targeting the lesion more safely. Several cytologists find US guidance unnecessary as a routinely used examination, which may lead to unsatisfactory smears and false negative results. This means not only a loss for the patient, but leads to a negative judgement of this diagnostic method. Our interventional cytology diagnostic team developed a working method resulting in excellent statistical results. In the followings we would like to share our experience refined the past two decades to restore the reputation of this diagnostic method.

[Significance of positive surgical margin in radical prostatectomy]. / A pozitív sebészi szél jelentõsége radikális prosztatektómia esetén.

The optimal oncological result of radical prostatectomy (RP) is complete removal of the prostate gland and seminal vesicles with negative surgical margins. Preoperative diagnostic biopsies are examined and reported by the pathologist according to standardized rules. Staging of the disease is based on modern preoperative image analysis, most commonly multiparametric MRI. Pathological assessment and reporting of RP specimens is based on the International Society of Uropathology guidelines issued by the 2009 Consensus Conference. Positive surgical margin (PSM) is reported by the pathologist in approximately 1/3rd of RP cases. PSM increases the risk of biochemical, local and systemic progression. Pseudo-whole mount assessment of these specimens is the basis for radio-pathological correlation, thus providing quality control for preoperative MRI as well as assisting preoperative image analysis, sampling and diagnostic workup.

Pretreatment MicroRNA Level and Outcome in Sorafenib-treated Hepatocellular Carcinoma.

Sorafenib represents the first effective targeted therapy for advanced stage hepatocellular carcinoma (HCC); however, adequate patient stratification regarding sorafenib-responsiveness is still missing. Our aim was to analyse the association between the pretreatment microRNA profile of HCC and patient survival under sorafenib treatment. Total RNA was extracted from diagnostic fine-needle aspiration biopsy (FNAB) cytological smears of 20 advanced stage HCC patients collected between June 2008 and July 2012. All patients underwent sorafenib administration after FNA. Clinicopathological and survival data were recorded. Fourteen frequently deregulated miRNAs in HCC (miR-17-5p, miR-18a, miR-21, miR-34a, miR-122, miR-195, miR-210, miR-214, miR-221, miR-222, miR-223, miR-224, miR-140, miR-328) were tested by qRT-PCR. NormFinder software was used to select proper miR (mir-140) as a reference. Satisfactory amount of total RNA was obtained from all the considered samples (mean 10.8 ± 9.3 µg, range 0.2-32.2 µg). Among the analysed miRNAs, high miR-214 expression was associated with smaller tumor size (p=0.019), whereas high miR-17-5p expression correlated with better Eastern Cooperative Oncology Group performance status (p=0.003). The survival analysis revealed that high miR-224 expression was associated with increased progression-free and overall survival (PFS p=0.029; OS p=0.012). Pretreatment microRNA profiling, especially miR-224 expression, might serve as an ancillary tool for the better assessment of expected survival rates for patients under sorafenib treatment.

The influence of expertise of the surgical pathologist to undergrading, upgrading, and understaging of prostate cancer in patients undergoing subsequent radical prostatectomy.

PURPOSE: The main objective of this retrospective study was to evaluate the influence of pathological experience in histological examination of prostate cancer (PCa) on preoperative understaging (UNS), undergrading (UNG), and upgrading (UPG). METHODS: Histopathological data of prostate biopsy (PB) and radical prostatectomy (RP) specimens of patients undergoing subsequent radical prostatectomy (n = 430) in our center were compared. Histological diagnoses of PB were provided either by corresponding academic pathology institute (Group 1: 322 patients) or by external (nonacademic) departments which had a lower number (≤ 100/year) of PCa histopathological evaluations (Group 2 108 patients). The rate of UNG, UPG, and UNS in both groups and also the effects of institutional learning curve were analyzed in terms of grading and staging. RESULTS: Significant difference was detected between Group 1 and Group 2 in average preoperative Gleason score (GS) values and in the rate of well, moderately, and poorly differentiated cancers as well. There was also a significant difference in the rate of UNG (29.1 vs. 56.5 %, p < 0.0001). The mean preoperative and postoperative GS in Group 1 was significantly lower in the first 50 than in the last 50 patients, but the rates of UNG, UPG, and UNS did not differ significantly between the groups. CONCLUSIONS: The experience of pathologists has direct influence on grading concordance and on UNG and UPG, between PB and RP specimen; however, it has no significant effect on complete preoperative understaging. The bigger pathological experience improves the sensitivity of the histological diagnostic process.